caa a22 4500 477081525 CHVBK 20180405111451.0 cr unu---uuuuu 170330e19961101xx s 000 0 eng 10.1007/BF02724049 doi (NATIONALLICENCE)springer-10.1007/BF02724049 Autocrine regulation of cell cycle progression in normal human keratinocytes [Elektronische Daten] [Geoffrey Curtin, David Bombick, David Doolittle] Summary: Removal of competence factors insulin and pituitary extract from the culture medium, concomitant with the addition of picomolar concentrations of the late-G1 inhibitor transforming growth factor-beta, effectively arrested cell cycle progression of normal human keratinocytes prior to their entry into the DNA synthesis phase; arrest continued for a minimum of 36 h following removal of unbound inhibitor and subsequent addition of factor-deficient medium. To demonstrate the reversibility of transforming growth factor-beta-induced arrest, two dissimilar cell populations were recruited to synthesize DNA in a predictable and reproducible manner; whereas the reinstatement of omitted competence factors induced noncycling cells to begin synthesizing DNA within 24 h, addition of keratinocyte-conditioned medium prompted an immediate progression of late-G1 cells into S phase. Studies to determine the extent that autocrine signaling regulates cell cycle progression revealed that nontransformed keratinocytes produce an endogenous factor required for DNA replication and that production of this progression factor required competence factors insulin and pituitary extract. Keratinocyte progression factor recruited late-G1 cells into S phase within 1-2 h, reversed transforming growth factor-beta-induced arrest in the presence of bound inhibitor, and elicited a calcium mobilization response consistent with receptor-mediated signaling. Hence, these studies demonstrate that G1 progression of nontransformed keratinocytes into S phase requires an endogenous progression factor and suggest that this factor may direct G1 progression by modulating the activity of a calcium-dependent kinase. Society for In Vitro Biology, 1996 skin epithelium nationallicence progression factor nationallicence calcium mobilization nationallicence Curtin Geoffrey Integrated Toxicology Program, Duke University Medical Center, 27710, Durham, North Carolina aut Bombick David Laboratory of Cellular and Molecular Biology, R. J. Reynolds Tobacco Co., 27102, Winston-Salem, North Carolina aut Doolittle David Integrated Toxicology Program, Duke University Medical Center, 27710, Durham, North Carolina aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 32/10(1996-11-01), 640-655 1071-2690 32:10<640 1996 32 11626 https://doi.org/10.1007/BF02724049 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02724049 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Curtin Geoffrey Integrated Toxicology Program, Duke University Medical Center, 27710, Durham, North Carolina aut NATIONALLICENCE 700 1- Bombick David Laboratory of Cellular and Molecular Biology, R. J. Reynolds Tobacco Co., 27102, Winston-Salem, North Carolina aut NATIONALLICENCE 700 1- Doolittle David Integrated Toxicology Program, Duke University Medical Center, 27710, Durham, North Carolina aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 32/10(1996-11-01), 640-655 1071-2690 32:10<640 1996 32 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer